巴利昔单抗在预防肾移植后排斥反应中的应用

目的:探讨巴利昔单抗诱导治疗预防肾移植后急性排斥反应的有效性和安全性。方法:在使用环孢素、霉酚酸酯及激素三联抗排斥的基础上,将42例肾移植受者随机分2组,每组各21例,试验组术前30min及术后d4各给予巴利昔单抗20mg+氯化钠注射液100mL,静脉滴注,对照组只使用氯化钠注射液静脉滴注。评价急性排斥反应的发生率、严重程度以及巴利昔单抗治疗的安全性。结果:试验组急性排斥反应发生率10%(2/21),发生时间(2.8±s0.8)mo;对照组发生率29%(6/21),发生时间(1.1±0.7)mo,早于试验组(P<0.01)且严重程度高于试验组。血肌酐恢复正常的时间试验组(4.0±0.7)d,对照组(7.8±1.6)d,P<0.01。不良反应发生率2组间差异无显著意义,P<0.05。结论:巴利昔单抗联合环孢素、霉酚酸酯和激素预防肾移植后急性排斥反应安全有效。     

巴利昔单抗联合鼠抗人CD3单克隆抗体在高致敏受者肾移植中的临床应用

目的:探讨巴利昔单抗与鼠抗人CD3单克隆抗体(OKT3)联合诱导在高致敏受者肾移植临床应用中的有效性及安全性。方法:术前2个月内群体反应性抗体(PRA)检测值均>50%的尸体供肾肾移植受者20例,其中9例受者接受巴利昔单抗联合OKT3免疫诱导(联合诱导组),11例受者接受OKT3常规免疫诱导(OKT3诱导组),均以他克莫司(Tac)+吗替麦考酚酯(MMF)+泼尼松(Pred)为基础免疫抑制方案,评估术后移植肾功能恢复情况、3个月内急性排斥反应发生率、1年内肺部感染发生率、1年人/肾存活率及移植肾功能。结果:联合诱导组、OKT3诱导组肾移植术后3个月内急性排斥反应发生率及术后1年内肺部感染发生率分别为11.1%vs.36.4%(P=0.319),11.1%vs.63.6%(P=0.028);联合诱导组患者术后1周内移植肾功能恢复正常比例明显高于OKT3诱导组(88.9%vs.27.3%,P=0.010);联合诱导组术后1年人/肾存活率均为100%,与OKT3诱导组(分别为90.9%、81.8%)比较,差异不显著(P=1.00和P=0.100);术后1年联合诱导组、OKT3诱导组血肌酐值分别为(105±24)、(97±22)μmol·L-1(P=0.437)。结论:巴利昔单抗联合OKT3进行免疫诱导,在预防高致敏受者术后早期排斥反应的同时,缩短了移植肾功能的恢复时间,是一种安全、有效的防治策略。     

二重血浆置换及免疫吸附联合IL-2受体单抗方案处理致敏肾移植受者的临床研究

目的:评估应用二重血浆置换(DFPP)、免疫吸附(IA)联合IL-2受体单抗方案处理致敏肾移植受者的临床效果。方法:将56例致敏肾移植受者分为2组,35例试验组应用DFPP、IA联合IL-2受体单抗方案,21例对照组未进行上述处理。采用酶联免疫吸附(ELISA)方法检测肾移植受者体内群体反应性抗体(PRA)水平,比较2组急性排斥反应(AR)和肾功能延迟恢复(DGF)的发生率,随访2组人/肾1a存活率及术后6个月和12个月的血肌酐情况。结果:试验组PRA明显下降,PRA降为阴性者14例;试验组与对照组术后AR发生率分别为28.6%、42.9%(P<0.05),DGF发生率分别为8.6%、14.3%(P>0.05),1a人存活率分别为100.0%、95.2%(P>0.05),移植肾1a存活率分别为94.3%、76.2%(P<0.05),随访6个月/12个月血肌酐分别为(115.2±16.6)/(121.2±28.6)μmol.L-1和(128.4±27.4)/(134.6±33.7)μmol.L-1(P<0.05)。结论:DFPP、IA联合IL-2受体单抗方案可选择性去除受者体内的致敏抗体,可降低致敏受者术后AR的发生率,提高术后肾移植受者1a移植肾存活率,术后6个月和12个月的血肌酐水平也较低。     

前列地尔对同种异体肾移植中早期肾功能的保护作用

目的 :探讨前列地尔对肾移植术后早期肾功能恢复的影响。方法 :对85例 (A组 )肾移植受者术中及术后2wk内每天应用前列地尔60μg,与同期276例 (B组)未应用前列地尔的肾移植受者进行对比。结果 :A组术后尿量(6d内)和内生肌酐清除率 (至少7d内 )均明显高于B组 (P<0 01) ,而血肌酐 (5d内)以及血流阻力指数 (14d内 )和肾功能延迟恢复的发生率则明显低于B组(P<0 01) ,但两组急性排斥反应发生率 (3mo内 )无显著性差异 (P>0 05)。结论 :肾移植术中及术后早期应用前列地尔有利于移植肾功能的恢复 ,但不降低急性排斥反应发生率。     

肾移植受者手术前后血清sICAM-1 sIL-2R sIL-10 Fas FasL水平的变化及意义

目的探讨肾移植受者手术前后血清可溶性细胞间黏附分子1(sICAM1)、可溶性白细胞介素2受体(sIL2R)、可溶性白细胞介素10(sIL10)、Fas、FasL水平的变化及意义。方法采用酶联免疫吸附试验(ELISA)检测14例肾移植受者手术前、术后1周及术后2周血清sICAM1、sIL2R、sIL10、Fas、FasL的定量,分析其变化与急性排斥反应和免疫抑制剂血药浓度的关系。结果肾移植术后血清sICAM1、sIL2R浓度在使用免疫抑制剂后均有不同程度的降低,发生排斥反应后2dsICAM1浓度有所升高。使用他克莫司受者术后1、2周时sIL2R浓度下降更明显,与使用环孢素受者比较具有统计学意义。sIL10术前检出1例,术后1周检出2例,术后2周检出2例;Fas术前检出4例,术后1周检出0例,术后2周检出2例。FasL术前检出11例,术后1周检出0例,术后2周检出7例,浓度较术前减低,未发现与排斥反应有关联。环孢素谷值浓度个体差异更大。结论血清sICAM1、sIL2R浓度的动态变化及手术前后的比值可以作为免疫抑制剂使用后免疫抑制状态的初步判定及鉴别排斥反应和免疫抑制剂肾中毒的指标之一。未发现在术前、术后2周内sIL10、Fas与排斥反应和免疫抑制剂相关。FasL在检出的受者中,手术后2周浓度有下降的趋势,未发现有与排斥反应有关的变化。     

肾移植术后长期应用硫氮唑酮对环孢素A用量和肾功能的影响

目的:观察钙通道阻滞药硫氮唑酮(Dil)长期应用对肾移植受者环孢素A(CsA)用量和肾功能的影响。方法:将Dil用于67例服用CsA的肾移植受者,以同期59例肾移植受者为对照,调整2组CsA血药浓度在治疗窗范围内,观察2组用药后36mo内CsA用量以及血肌酐变化。结果:术后第12、24、36moDil组每例CsA用量较对照组同期平均少14353、9656、7817mg;术后12mo内2组血肌酐无显著性差异,以后对照组血肌酐水平上升较快,术后18mo～36mo,Dil组血肌酐水平明显低于对照组同期(P<0.05)。结论:肾移植术后长期应用Dil不仅可明显减少肾移植受者的CsA用量,而且可以改善移植肾功能。     

肾移植受者因环孢素所致药源性疾病而转换为他克莫司的回顾性研究

目的探讨肾移植受者在以环孢素为基础的免疫抑制剂方案治疗期间发生药源性疾病(DID)后,将环孢素切换为他克莫司后对疗效的影响。方法通过收集92例将环孢素切换为他克莫司的肾移植受者的临床资料,分析切换后1年内环孢素所致DID改善的情况。结果与未切换方案时相比,发生急性排异反应(AR)和爬行肌酐(CScr)的肾移植受者在切换方案后1、3、6和12个月的血肌酐(Scr)和尿素氮(BUN)均下降(P<0.05或0.01);发生药物性肝损伤(DILI)者在切换方案后1、3、6和12个月的直接胆红素(DB)、总胆红素(TB)均下降(P<0.05或0.01),在切换方案后12个月时谷丙转氨酶(ALT)降低(P<0.05);牙龈增生(GH)在切换方案1个月后逐渐消失。但切换方案后肾移植受者空腹血糖(FPG)却逐渐升高,并在12个月时显著升高(P<0.05)。结论血糖正常的肾移植受者,如发生与环孢素有关的AR、CScr、DILI和(或)GH等严重DID,将环孢素切换为他克莫司,可有效提高肾移植受者的生存质量和生存期。     

利妥昔单抗联合氟达拉滨、环磷酰胺治疗慢性淋巴细胞白血病的临床观察

目的:观察利妥昔单抗联合氟达拉滨、环磷酰胺治疗慢性淋巴细胞白血病(CLL)的临床疗效和安全性。方法:140例CLL患者按随机数字表法分为氟达拉滨联合环磷酰胺组(FC组,78例)和利妥昔单抗联合氟达拉滨、环磷酰胺(FCR组,62例)。FC组患者给予氟达拉滨25 mg/(m2·d)加入0.9%氯化钠注射液100 ml,d1-3静脉滴注,qd;环磷酰胺250 mg/(m2·d)加入0.9%氯化钠注射液100 ml,d1-3静脉滴注,qd。FCR组患者给予氟达拉滨25 mg/(m2·d)加入0.9%氯化钠注射液100 ml,d2-4静脉滴注,qd;环磷酰胺250 mg/(m2·d)加入0.9%氯化钠注射液100 ml,d2-4静脉滴注,qd;利妥昔单克隆抗375 mg/m2加入0.9%氯化钠注射液中稀释至1 mg/ml,d1静脉滴注,qd。28 d为1个周期,治疗4个周期后评价疗效。观察两组患者毒性反应及随访12个月的生存率。结果:FCR组患者总有效率显著高于FC组(P<0.05)。两组患者毒性反应总发生例数、短期生存率比较,差异无统计学意义(P>0.05)。结论:利妥昔单抗联合氟达拉滨、环磷酰胺治疗CLL疗效优于氟达拉滨联合环磷酰胺,安全性较好。     

利妥昔单抗治疗原发性IgA肾病的疗效及安全性分析

目的 评价利妥昔单抗治疗原发性IgA肾病的疗效及安全性。方法 回顾性分析自2019年1月至2021年12月郑州大学第一附属医院经肾活检确诊且接受利妥昔单抗治疗的原发性IgA肾病患者的临床资料,观察利妥昔单抗治疗后患者缓解率、复发率及不良事件等。结果 共纳入30例患者,与基线相比,利妥昔单抗治疗后患者血清白蛋白水平上升(P<0.05);24小时尿蛋白定量、尿蛋白/肌酐比值均显著下降(P<0.01);血清肌酐、肾小球滤过率无明显变化(P>0.05)。按照病理类型分为3组,其中IgA肾病(IgAN)组8例,IgA肾病伴微小病变肾病(IgAN-MCD)组10例,IgA肾病伴膜性肾病(IgAN-MN)组12例。使用Kaplan-Meier生存曲线比较三组缓解率,三组的中位缓解时间分别为212 d、29 d和95 d。IgAN-MCD组与IgAN-MN组累积缓解率差异有统计学意义(χ²=5.767,P=0.016),IgAN组与IgAN-MCD组、IgAN组与IgAN-MN组累积缓解率差异均无统计学意义。30例患者接受利妥昔单抗治疗前复发率为76.77%(2...     

海洛因依赖者血清细胞因子含量与红细胞免疫功能的变化及其相互关系

目的·· :探讨海洛因依赖者血清细胞因子含量与红细胞免疫功能的变化及其关系。方法·· :采用双抗夹心ELISA法对50例海洛因依赖者血清白细胞介素2(IL -2)、可溶性白细胞介素2受体 (sIL -2R)和干扰素 -γ(IFN -γ)进行测定 ;检测红细胞C3b受体花环 (RBC -C3bRR)、红细胞免疫复合物花环 (RBC -ICR)、粘附增强因子活性(RFER)及抑制因子活性 (RFIR),观察海洛因依赖者红细胞免疫功能的变化。结果·· :海洛因依赖者血清IL -2、IFN -γ水平显著低于正常组 (P<0.01),sIL -2R水平比正常组明显上升 (P<0.01) ;海洛因依赖者RBC -C3bRR、RFER明显下降 (P<0.01)。血清IL -2和IFN -γ含量与RBC -C3bRR、RFER正相关(r=0.86,P<0.01);血清sIL -2R水平与RBC -C3bRR、RFER负相关(r= -0.88,P<0.01)。结论·· :海洛因依赖者细胞因子 (IL -2、IFN -γ)水平及红细胞免疫功能均属低下 ,且二者密切相关。     

A review of interleukin-2 receptor antagonists in solid organ transplantation.

Daclizumab and basiliximab, engineered human IgG monoclonal antibodies to the interleukin-2 (IL-2) receptor alpha-subunit, were approved to prevent acute rejection after renal transplantation. Daclizumab was studied in adult and pediatric renal allograft recipients, liver allograft recipients, and calcineurin-sparing protocols in renal transplant recipients. Basiliximab was studied in renal allograft recipients and subgroups of recipients of living-related and cadaveric transplants, and in patients with diabetes mellitus. Both agents reduced acute rejection and were associated with few adverse effects. However, information regarding their long-term effects on infection, malignancy, chronic rejection, and patient survival must be available before a final decision is made regarding their proper administration. We propose that a likely role the drugs will play in the field of solid organ transplantation is in new protocols that allow sparing of other more toxic immunosuppressive agents.     

Basiliximab: a review of its use as induction therapy in renal transplantation

Basiliximab (Simulect), a chimeric (human/murine) monoclonal antibody, is indicated for the prevention of acute organ rejection in adult and paediatric renal transplant recipients in combination with other immunosuppressive agents.Basiliximab significantly reduced acute rejection compared with placebo in renal transplant recipients receiving dual- (cyclosporin microemulsion and corticosteroids) or triple-immunotherapy (azathioprine- or mycophenolate mofetil-based); graft and patient survival rates at 12 months were similar. Significantly more basiliximab than placebo recipients were free from the combined endpoint of death, graft loss or acute rejection 3 years, but not 5 years, after transplantation.The incidence of adverse events was similar in basiliximab and placebo recipients, with no increase in the incidence of infection, including cytomegalovirus (CMV) infection. Malignancies or post-transplant lymphoproliferative disorders after treatment with basiliximab were rare, with a similar incidence to that seen with placebo at 12 months or 5 years post-transplantation. Rare cases of hypersensitivity reactions to basiliximab have been reported.The efficacy of basiliximab was similar to that of equine antithymocyte globulin (ATG) and daclizumab, and similar to or greater than that of muromonab CD3. Basiliximab was as effective as rabbit antithymocyte globulin (RATG) in patients at relatively low risk of acute rejection, but less effective in high-risk patients. Numerically or significantly fewer patients receiving basiliximab experienced adverse events considered to be related to the study drug than ATG or RATG recipients. The incidence of infection, including CMV infection, was similar with basiliximab and ATG or RATG.Basiliximab plus baseline immunosuppression resulted in no significant differences in acute rejection rates compared with baseline immunosuppression with or without ATG or antilymphocyte globulin in retrospective analyses conducted for small numbers of paediatric patients. Limited data from paediatric renal transplant recipients suggest a similar tolerability profile to that in adults. Basiliximab appears to allow the withdrawal of corticosteroids or the use of corticosteroid-free or calcineurin inhibitor-sparing regimens in renal transplant recipients.Basiliximab did not increase the overall costs of therapy in pharmacoeconomic studies.CONCLUSION: Basiliximab reduces acute rejection without increasing the incidence of adverse events, including infection and malignancy, in renal transplant recipients when combined with standard dual- or triple-immunotherapy. The overall incidence of death, graft loss or acute rejection was significantly reduced at 3 years; there was no significant difference for this endpoint 5 years after transplantation. Malignancy was not increased at 5 years. The overall efficacy, tolerability, ease of administration and cost effectiveness of basiliximab make it an attractive option for the prophylaxis of acute renal transplant rejection.     

Economic implications of the use of basiliximab in addition to triple immunosuppressive therapy in renal allograft recipients: a UK perspective

OBJECTIVE: To compare resource use and costs in renal transplant recipients treated with basiliximab or placebo plus triple immunosuppressive therapy. DESIGN: International randomised, double-blind, placebo-controlled trial; economic evaluation undertaken alongside the efficacy trial. The economic evaluation was performed from a UK National Health Service hospital perspective. SETTING: 31 centres in 12 countries. PARTICIPANTS: 345 renal transplant recipients were enrolled; 340 were randomised (basiliximab 168; placebo 172) and included in the intention-to-treat analysis. INTERVENTION: Treatment with placebo or basiliximab (20mg intravenous bolus) on day 0 and day 4 after transplantation. MAIN OUTCOME MEASURES: Resource utilisation in multiple categories and treatment costs for basiliximab and placebo-treated patients during the 6-month post-transplantation period. RESULTS: No statistically significant differences were found in any of the economically important categories of resource use or in the mean cost of treatment per person across the whole trial. The mean cost of treatment, including the cost of basiliximab, was pound 16 095 for basiliximab recipients and pound 15 864 (1997/1998 costs) for placebo recipients, a mean difference of pound 231 (95% CI: - pound 1983 to pound 2446), which was not significant. Basiliximab treatment led to a significant reduction in acute rejection episodes (basiliximab 20.8%; placebo 34.9%; p = 0.005). CONCLUSIONS: Basiliximab therapy confers a significant clinical benefit to renal transplant recipients without increasing overall treatment costs.     

儿童慢性乙型肝炎细胞免疫功能及胸腺素疗效

目的　探讨慢性乙型肝炎(CHB)患儿细胞免疫功能及胸腺素疗效。方法　6 0例CHB患儿随机分为常规组(予常规治疗)和胸腺素组(在常规治疗基础上+胸腺素) ,并以6 0例健康儿童作为正常对照组。于治疗前、疗程结束后1mo检测T细胞亚群(CD+ 3 、CD+ 4 、CD+ 8)、血清白细胞介素2 (IL 2 )及可溶性白细胞介素2受体(sIL 2R)水平;定期复查肝功能、乙肝标志物和HBV DNA。结果　与正常对照组比较,CHB组CD+ 3 与CD+ 4 的百分率、CD+ 4 /CD+ 8及血清IL 2水平明显降低(P均<0 0 1) ,CD+ 8百分率及血清sIL 2R水平明显升高(P均<0 0 1) ;与常规组比较,胸腺素组血清ALT明显下降(P <0 0 1) ,ALT复常时间明显缩短(P <0 0 1) ,HBeAg转阴率明显上升(P <0 0 5 ) ,各免疫学指标明显恢复,差异均有统计学意义(P <0 0 1或P <0 0 5 )。结论　CHB患儿细胞免疫功能低下,胸腺素能增强细胞免疫功能,有利于病毒清除和肝功能的恢复     

Anti-interleukin-2 receptor antibodies for the prevention of rejection in pediatric renal transplant patients: current status

The anti-interleukin-2 receptor (anti-IL-2R) antibody therapy is an exciting approach to the prevention of acute rejection after renal allograft transplantation whereby immunosuppression is exerted by a selective and competitive inhibition of IL-2-induced T cell proliferation, a critical pathway of allorecognition. The anti-IL-2R antibodies specifically block the alpha-subunit of the IL-2R on activated T cells, and prevent T cell proliferation and activation of the effector arms of the immune system. The anti-IL-2R antibodies are used as induction therapy, immediately after renal transplantation, for prevention of acute cellular rejection in children and adults. During acute rejection, the IL-2Ralpha chain is no longer expressed on T cells; thus, the antibodies cannot be used to treat an existing acute rejection. Two anti-IL-2R monoclonal antibodies are currently in clinical use: daclizumab and basiliximab. In placebo-controlled phase III clinical trials in adults, daclizumab and basiliximab in combination with calcineurin inhibitor-based immunosuppression, significantly reduced the incidence of acute rejection and corticosteroid-resistant acute rejection without increasing the risk of infectious or malignant complications, and neither antibody was associated with the cytokine-release syndrome. Children who receive calcineurin inhibitors and corticosteroids for maintenance immunosuppression, as well as children who receive augmented immunosuppression to treat acute rejection, are at increased risk of growth impairment, hypertension, hyperlipidemia, lymphoproliferative disorders, diabetes mellitus, and cosmetic changes. In older children, the cosmetic adverse effects frequently reduce compliance with the treatment, and subsequently increase the risk of allograft loss. Being effective and well tolerated in children, the anti-IL-2R antibodies reduce the need for calcineurin inhibitors while maintaining the overall efficacy of the regimen; thus, the anti-IL-2R antibodies increase the safety margin (less toxicity, fewer adverse effects) of the baseline immunosuppression. Secondly, the anti-IL-2R antibodies decrease the need for corticosteroids and muromonab CD3 (OKT3) in children as a result of decreased incidence of acute rejection. The recommended pediatric dose of daclizumab is 1 mg/kg intravenously every 14 days for five doses, with the first dose administered within 24 hours pre-transplantation. This administration regimen maintains daclizumab levels necessary to completely saturate the IL-2Ralpha (5-10 microg/mL) in children for at least 12 weeks.The recommended pediatric dose of basiliximab for recipients <35 kg is 10 mg, and 20 mg for recipients > or =35 kg, intravenously on days 0 and 4 post-transplantation. This administration regimen maintains basiliximab levels necessary to completely saturate the IL-2Ralpha (>0.2 microg/mL) in children for at least 3 weeks.     

慢性肝病患者血清白介素-6及其受体检测的临床意义

目的：观察慢性肝病患者血清白介素-6（IL-6）和可溶性IL-6受体（sIL-6R）的变化。方法：应用酶联免疫吸附试验（EIL-SA）检测慢性肝炎患者86例、肝炎后肝硬化患者18例和20例健康对照组血清中IL-6和sIL-6R水平。结果：慢性肝炎患者血清IL-6和sIL-6R含量均显著高于健康对照组（P〈0．01），其中肝炎后肝硬化组上述2参数高于慢性肝炎组；慢性肝炎组中的上述2参数显示为：重度〉中度〉轻度．各组间差异有显著性（P〈0．05或P〈0．01）：慢性肝病组血清IL-6和sIL-6R水平之间呈正相关（r=0．481，P〈0．05），IL-6和sIL-6R水平与血清总胆红素水平间亦呈正相关（r=-0．417，0．418，P〈0．01），与ALT之间无明显相关性（r=0．173，0．182，P〉0．05）。结论：血清IL-6和sIL-6R与慢性肝病的病情演变有关．对其预后有一定指导意义。     

76例戊肝病人血清白细胞介素-2受体动态检测及临床意义

目的 为了解血清白细胞介素-2受体(sIL-2R)在戊肝病程中的变化及意义。方法 动态观察了76例戊肝患者急性期及恢复期的sIL-2R水平,并与同期血清ALT及T-Bil水平进行了对比,以健康献血员作对照。结果 戊肝各期sIL-2R水平均高于对照组,戊肝极期sIL-2R水平显著高于恢复期(P<0.01～0.05),戊肝各期sIL-2R水平与ALT及T-Bil呈显著正相关(r=0.58,P<0.ol;r=0.40,P相似文献